12/22/2023 0 Comments Noti restriction enzyme![]() Yet, few functional markers of CSF-cNs related to their sensory or secretory functions have been identified in this species. The zebrafish has emerged as an ideal model organism to study the development 13, 29, 30, the morphology and physiological roles of CSF-cNs in vivo due to its transparency at early stages 12, 15, 37. In addition, some secreted compounds have been previously reported in a restricted number of spinal CSF-cNs, such as the somatostatin 33, 34 or serotonin 35, 36. In mouse, spinal CSF-cNs were recently shown to originate from the p3 and p2 progenitor domains 26. In zebrafish, CSF-cNs are subdivided into the ventral population, referred to as KA”, originating from the progenitor domain p3 and a dorsal population, referred to as KA’, originating from pMN 29, 30. In particular, these cells originate from distinct progenitor domains and are specified differentially by several cascades of transcription factors 26, 29– 32. There is evidence that spinal CSF-cNs do not constitute a homogeneous population of neurons. Although the physiological variations of pH and osmolarity in the CSF are not well known, these observations suggest that CSF-cNs could be interoceptors modulated by chemical and/or mechanical cues from the CSF 23. ![]() The opening of the PKD2L1 channel is modulated by variations in pH 27 and osmolarity 28. PKD2L1, originally identified as the sour taste receptor in the taste buds, has been found in the spinal CSF-cNs of mouse 11, 13, 25, 26, zebrafish and macaques 13. In this regard, the polycystic kidney disease 2 like 1 (PKD2L1) channel also called TRPP3 22, which belongs to the Transient Potential Receptor (TRP) family, appears as a robust candidate to label CSF-cNs 11, 13, 23, 24. One essential step to understand spinal CSF-cN functions lies in identifying specific markers for these cells. In the vertebrate spinal cord, CSF-cNs reside around the central canal 9– 15 and project an apical extension in contact with the CSF 8, 16– 18 and have a locally-projecting axon 14, 19, 20 that contacts other spinal neurons 12, 15, 21. Cerebrospinal fluid-contacting neurons (CSF-cNs) are precisely located at the interface between the CSF and the neuronal circuits 7, 8. These observations suggest that chemical or mechanical cues from the CSF may act on neurons in the brain and spinal cord. Multiple studies indicate that the CSF also conveys signals affecting the development and output functions of the CNS, such as feeding, sleep, and locomotion 2– 6. It has classically been assumed that the CSF ensures the homeostasis of the CNS 1. The cerebrospinal fluid (CSF) is a complex solution circulating around the central nervous system (CNS). This work opens novel avenues to understand how these subtypes may carry distinct functions related to development of the spinal cord, locomotion and posture. Altogether our study demonstrates that the developmental origins of spinal CSF-cNs give rise to two distinct functional populations of sensory neurons. We show in zebrafish larva that the expression of specific markers, the morphology of the apical extension and axonal projections, as well as the neuronal targets contacted by CSF-cN axons, distinguish the two CSF-cN subtypes. Here we ask whether these neurons with different developmental origins differentiate into cells types with different functional properties. In zebrafish and mouse spinal CSF-cNs originate from two distinct progenitor domains characterized by distinct cascades of transcription factors. In the spinal cord, these GABAergic neurons expressing the PKD2L1 channel extend an apical extension into the CSF and an ascending axon in the spinal cord. Cerebrospinal fluid-contacting neurons (CSF-cNs) situated at the interface between the CSF and the CNS are ideally located to convey such information to local networks. How such cues are detected and relayed to the CNS remains elusive. Chemical and mechanical cues from the cerebrospinal fluid (CSF) can affect the development and function of the central nervous system (CNS).
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